We have continued to characterize the regulatory mechanisms related to hypothalamic-pituitary activity in rhesus monkeys and man. (1) The extent of cortisol suppressibility in an individual monkey in response to a low dose of dexamethasone has been demonstrated to be reproducible over time. (2) A positive relationship has been established between the extent of dexamethasone suppressibility and behavioral arousal. (3) The physostigmine behavioral syndrome is accompanied by increases in plasma ACTH which positively correlate with previously observed plasma beta-endorphin increases but not with cortisol elevations. (4) The current knowledge of the neuropharmacology of neuroendocrine regulatory mechanisms in affective disturbances and their assessment by pharmacological challenge strategies was formally reviewed.